PMID- 17664281
OWN - NLM
STAT- MEDLINE
DCOM- 20080122
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 27
IP  - 19
DP  - 2007 Oct
TI  - Cyclic AMP-stimulated interaction between steroidogenic factor 1 and 
      diacylglycerol kinase theta facilitates induction of CYP17.
PG  - 6669-85
AB  - In the human adrenal cortex, adrenocorticotropin (ACTH) activates CYP17 
      transcription by promoting the binding of the nuclear receptor steroidogenic 
      factor 1 (SF1) (Ad4BP, NR5A1) to the promoter. We recently found that sphingosine 
      is an antagonist for SF1 and inhibits cyclic AMP (cAMP)-dependent CYP17 gene 
      transcription. The aim of the current study was to identify phospholipids that 
      bind to SF1 and to characterize the mechanism by which ACTH/cAMP regulates the 
      biosynthesis of this molecule(s). Using tandem mass spectrometry, we show that in 
      H295R human adrenocortical cells, SF1 is bound to phosphatidic acid (PA). 
      Activation of the ACTH/cAMP signal transduction cascade rapidly increases nuclear 
      diacylglycerol kinase (DGK) activity and PA production. PA stimulates 
      SF1-dependent transcription of CYP17 reporter plasmids, promotes coactivator 
      recruitment, and induces the mRNA expression of CYP17 and several other 
      steroidogenic genes. Inhibition of DGK activity attenuates the binding of SF1 to 
      the CYP17 promoter, and silencing of DGK-theta expression inhibits cAMP-dependent 
      CYP17 transcription. LXXLL motifs in DGK-theta mediate a direct interaction of 
      SF1 with the kinase and may facilitate binding of PA to the receptor. We conclude 
      that ACTH/cAMP stimulates PA production in the nucleus of H295R cells and that 
      this increase in PA concentrations facilitates CYP17 induction.
FAU - Li, Donghui
AU  - Li D
AD  - School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
FAU - Urs, Aarti N
AU  - Urs AN
FAU - Allegood, Jeremy
AU  - Allegood J
FAU - Leon, Adam
AU  - Leon A
FAU - Merrill, Alfred H Jr
AU  - Merrill AH Jr
FAU - Sewer, Marion B
AU  - Sewer MB
LA  - eng
GR  - GM069338/GM/NIGMS NIH HHS/United States
GR  - R56 GM073241/GM/NIGMS NIH HHS/United States
GR  - U54 GM069338/GM/NIGMS NIH HHS/United States
GR  - R01 GM073241/GM/NIGMS NIH HHS/United States
GR  - GM073241/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070730
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Isoenzymes)
RN  - 0 (NR5A1 protein, human)
RN  - 0 (Phosphatidic Acids)
RN  - 0 (Phospholipids)
RN  - 0 (Steroidogenic Factor 1)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
RN  - EC 2.7.7.- (RNA Polymerase II)
SB  - IM
MH  - Adrenal Cortex/cytology/physiology
MH  - Adrenocorticotropic Hormone/metabolism
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cyclic AMP/*metabolism
MH  - Diacylglycerol Kinase/genetics/*metabolism
MH  - *Enzyme Induction
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - Humans
MH  - Isoenzymes/genetics/*metabolism
MH  - Phosphatidic Acids/metabolism
MH  - Phospholipids/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA Polymerase II/metabolism
MH  - Signal Transduction/*physiology
MH  - Steroid 17-alpha-Hydroxylase/genetics/*metabolism
MH  - Steroidogenic Factor 1/genetics/*metabolism
MH  - Two-Hybrid System Techniques
PMC - PMC2099220
EDAT- 2007/08/01 09:00
MHDA- 2008/01/23 09:00
PMCR- 2008/02/01
CRDT- 2007/08/01 09:00
PHST- 2007/08/01 09:00 [pubmed]
PHST- 2008/01/23 09:00 [medline]
PHST- 2007/08/01 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - MCB.00355-07 [pii]
AID - 0355-07 [pii]
AID - 10.1128/MCB.00355-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2007 Oct;27(19):6669-85. doi: 10.1128/MCB.00355-07. Epub 2007 Jul 
      30.